Novel electrode design for biosensor

ABSTRACT

A test strip for measuring a signal of interest in a biological fluid when the test strip is mated to an appropriate test meter, wherein the test strip and the test meter include structures to verify the integrity of the test strip traces, to measure the parasitic resistance of the test strip traces, and to provide compensation in the voltage applied to the test strip to account for parasitic resistive losses in the test strip traces. In addition, conductive traces are positioned to ensure structural interrogation of all electrodes and traces present upon the test strip.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/581,002, filed Jun. 18, 2004. This application is acontinuation-in-part of prior application Ser. No. unknown, filed Oct.8, 2004 entitled “SYSTEM AND METHOD FOR QUALITY ASSURANCE OF A BIOSENSORTEST STRIP.” This application is also related to application Ser. No.10/871,937 filed Jun. 18, 2004, and which is incorporated herein byreference in its entirety.

TECHNICAL FIELD

The present invention relates to an apparatus for use in measuringsignals such as those related to concentrations of an analyte (such asblood glucose) in a biological fluid as well as those related tointerferants (such as hematocrit and temperature in the case of bloodglucose) to analyte concentration signals. The invention relates moreparticularly to a system and method for quality assurance of a biosensortest strip.

BACKGROUND

Measuring the concentration of substances in biological fluids is animportant tool for the diagnosis and treatment of many medicalconditions. For example, the measurement of glucose in body fluids, suchas blood, is crucial to the effective treatment of diabetes.

Diabetic therapy typically involves two types of insulin treatment:basal, and meal-time. Basal insulin refers to continuous, e.g.time-released insulin, often taken before bed. Meal-time insulintreatment provides additional doses of faster acting insulin to regulatefluctuations in blood glucose caused by a variety of factors, includingthe metabolization of sugars and carbohydrates. Proper regulation ofblood glucose fluctuations requires accurate measurement of theconcentration of glucose in the blood. Failure to do so can produceextreme complications, including blindness and loss of circulation inthe extremities, which can ultimately deprive the diabetic of use of hisor her fingers, hands, feet, etc.

Multiple methods are known for determining the concentration of analytesin a blood sample, such as, for example, glucose. Such methods typicallyfall into one of two categories: optical methods and electrochemicalmethods. Optical methods generally involve spectroscopy to observe thespectrum shift in the fluid caused by concentration of the analyte,typically in conjunction with a reagent that produces a known color whencombined with the analyte. Electrochemical methods generally rely uponthe correlation between a current (Amperometry), a potential(Potentiometry) or accumulated charge (Coulometry) and the concentrationof the analyte, typically in conjunction with a reagent that producescharge-carriers when combined with the analyte. See, for example, U.S.Pat. No. 4,233,029 to Columbus, U.S. Pat. No. 4,225,410 to Pace, U.S.Pat. No. 4,323,536 to Columbus, U.S. Pat. No. 4,008,448 to Muggli, U.S.Pat. No. 4,654,197 to Lilja et al., U.S. Pat. No. 5,108,564 to Szuminskyet al., U.S. Pat. No. 5,120,420 to Nankai et al., U.S. Pat. No.5,128,015 to Szuminsky et al., U.S. Pat. No. 5,243,516 to White, U.S.Pat. No. 5,437,999 to Diebold et al., U.S. Pat. No. 5,288,636 toPollmann et al., U.S. Pat. No. 5,628,890 to Carter et al., U.S. Pat. No.5,682,884 to Hill et al., 5,727,548 to Hill et al., U.S. Pat. No.5,997,817 to Crismore et al., U.S. Pat. No. 6,004,441 to Fujiwara etal., U.S. Pat. No. 4,919,770 to Priedel, et al., and U.S. Pat. No.6,054,039 to Shieh, which are hereby incorporated in their entireties.The biosensor for conducting the tests is typically a disposable teststrip having a reagent thereon that chemically reacts with the analyteof interest in the biological fluid. The test strip is mated to anondisposable test meter such that the test meter can measure thereaction between the analyte and the reagent in order to determine anddisplay the concentration of the analyte to the user.

FIG. 1 schematically illustrates a typical prior art disposablebiosensor test strip, indicated generally at 10 (see, for example, U.S.Pat. Nos. 4,999,582 and 5,438,271, assigned to the same assignee as thepresent application, and incorporated herein by reference). The teststrip 10 is formed on a nonconductive substrate 12, onto which areformed conductive areas 14,16. A chemical reagent 18 is applied over theconductive areas 14,16 at one end of the test strip 10. The reagent 18will react with the analyte of interest in the biological sample in away that can be detected when a voltage potential is applied between themeasurement electrodes 14 a and 16 a.

The test strip 10 therefore has a reaction zone 20 containing themeasurement electrodes 14 a,16 a that comes into direct contact with asample that contains an analyte for which the concentration in thesample is to be determined. In an amperometric or coulometricelectrochemical measurement system, the measurement electrodes 14 a,16 ain the reaction zone 20 are coupled to electronic circuitry (typicallyin a test meter (not shown) into which the test strip 10 is inserted, asis well known in the art) that supplies an electrical potential to themeasurement electrodes and measures the response of the electrochemicalsensor to this potential (e.g. current, impedance, charge, etc.). Thisresponse is proportional to the analyte concentration.

The test meter contacts the test strip 10 at contact pads 14 b,16 b in acontact zone 22 of the test strip 10. Contact zone 22 is locatedsomewhat remotely from measurement zone 20, usually (but not always) atan opposite end of the test strip 10. Conductive traces 14 c,16 c couplethe contact pads 14 b,16 b in the contact zone 22 to the respectivemeasurement electrodes 14 a,16 a in the reaction zone 20.

Especially for biosensors 10 in which the electrodes, traces and contactpads are comprised of electrically conductive thin films (for instance,noble metals, carbon ink, and silver paste, as non-limiting examples),the resistivity of the conductive traces 14 c,16 c that connect thecontact zone 22 to the reaction zone 20 can amount to several hundredOhms or more. This parasitic resistance causes a potential drop alongthe length of the traces 14 c,16 c, such that the potential presented tothe measurement electrodes 14 a,16 a in the reaction zone 20 isconsiderably less than the potential applied by the test meter to thecontact pads 14 b,16 b of the test strip 10 in the contact zone 22.Because the impedance of the reaction taking place within the reactionzone 20 can be within an order of magnitude of the parasitic resistanceof the traces 14 c,16 c, the signal being measured can have asignificant offset due to the I-R (current x resistance) drop induced bythe traces. If this offset varies from test strip to test strip, thennoise is added to the measurement result. Furthermore, physical damageto the test strip 10, such as abrasion, cracks, scratches, chemicaldegradation, etc. can occur during manufacturing, shipping, storageand/or user mishandling. These defects can damage the conductive areas14,16 to the point that they present an extremely high resistance oreven an open circuit. Such increases in the trace resistance can preventthe test meter from performing an accurate test.

SUMMARY

A test strip for measuring a signal of interest in a biological fluidwhen the test strip is mated to an appropriate test meter, wherein thetest strip and the test meter include structures to verify the integrityof the test strip traces, to measure the parasitic resistance of thetest strip traces, and to provide compensation in the voltage applied tothe test strip to account for parasitic resistive losses in the teststrip traces. In addition, conductive traces are positioned to ensurestructural interrogation of all electrodes and traces present upon thetest strip.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be further described, by way of example only, withreference to the accompanying drawings, in which:

FIG. 1 is schematic plan view of a typical prior art test strip for usein measuring the concentration of an analyte of interest in a biologicalfluid.

FIG. 2 is a schematic plan view of a first embodiment test stripaccording to the present invention.

FIG. 3 is a schematic diagram of a first embodiment electronic testcircuit for use with the first embodiment test strip of FIG. 2.

FIG. 4 is an exploded assembly view of a second typical test strip foruse in measuring the concentration of an analyte of interest in abiological fluid.

FIG. 5 illustrates a view of an ablation apparatus suitable for use withthe present invention.

FIG. 6 is a view of the laser ablation apparatus of FIG. 5 showing asecond mask.

FIG. 7 is a view of an ablation apparatus suitable for use with thepresent invention.

FIG. 8 is a schematic plan view of a second embodiment test stripaccording to the present invention.

FIG. 9 is a schematic diagram of a second embodiment electronic testcircuit for use with the second embodiment test strip of FIG. 8.

FIG. 10 is a schematic diagram of a third embodiment electronic testcircuit for use with the second embodiment test strip of FIG. 8.

FIG. 11 is a schematic plan view of a third embodiment of a test strip.

FIG. 12 is a schematic plan view of a fourth embodiment of a test strip.

DETAILED DESCRIPTION OF THE SELECTED EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to the embodiment illustrated inthe drawings, and specific language will be used to describe thatembodiment. It will nevertheless be understood that no limitation of thescope of the invention is intended. Alterations and modifications in theillustrated device, and further applications of the principles of theinvention as illustrated therein, as would normally occur to one skilledin the art to which the invention relates are contemplated, are desiredto be protected. In particular, although the invention is discussed interms of a blood glucose meter, it is contemplated that the inventioncan be used with devices for measuring other analytes and other sampletypes. Such alternative embodiments require certain adaptations to theembodiments discussed herein that would be obvious to those skilled inthe art.

Although the system and method of the present invention may be used withtest strips having a wide variety of designs and made with a widevariety of construction techniques and processes, a first embodimentelectrochemical test strip of the present invention is illustratedschematically in FIG. 2, and indicated generally at 200. Portions oftest strip 200 which are substantially identical to those of test strip10 are marked with like reference designators. Referring to FIG. 2, thetest strip 200 comprises a bottom substrate 12 formed from an opaquepiece of 350 μm thick polyester (such as Melinex 329 available fromDuPont) coated on its top surface with a 50 nm conductive gold layer(for instance by sputtering or vapor deposition, by way of non-limitingexample). Electrodes, connecting traces and contact pads therefor arethen patterned in the conductive layer by, for example, a laser ablationprocess. One embodiment of a laser ablation process is performed bymeans of an excimer laser which passes through a chrome-on-quartz mask.The mask pattern defined by chrome causes parts of the laser field to bereflected while allowing other parts of the field to pass through thequartz, creating a pattern on the gold which is evaporated wherecontacted by the laser light. The laser ablation process is described ingreater detail hereinbelow. For example, working 214 a, counter 216 a,and counter sense 224 a electrodes may be formed as shown and coupled torespective measurement contact pads 214 b, 216 b and 224 b by means ofrespective traces 214 c, 216 c and 224 c. These contact pads 214 b, 216b and 224 b provide a conductive area upon the test strip 200 to becontacted by a connector contact of the test meter (not shown) once thetest strip 200 is inserted into the test meter, as is well known in theart.

FIGS. 2 and 3 illustrate an embodiment of the present invention thatimproves upon the prior art test strip designs by allowing forcompensation of parasitic I-R drop in the counter electrode line of thetest strip. It will be appreciated that the test strip 200 of FIG. 2 issubstantially identical to the prior art test strip 10 of FIG. 1, exceptfor the addition of the counter sense electrode 224 a, contact pad 224b, and trace 224 c. Provision of the counter sense line 224 allows thetest meter (as described hereinbelow) to compensate for parasiticresistance between the contact pads 216 b,224 b. Note that theembodiment of FIG. 2 when used with the circuit of FIG. 3 onlycompensates for the I-R drop on the counter electrode side of the teststrip 200. Parasitic resistance on the working electrode side of thetest strip 200 cannot be detected using this circuitry, although itcould be replicated on the working electrode side if desired, as will beapparent to those skilled in the art with reference to the presentdiclosure. Further methods for compensating for parasitic resistance onboth the working and counter sides of the test strip are presentedhereinbelow. The counter sense line of FIG. 2 therefore allows the testmeter to compensate for any parasitic resistance potential drop in thecounter line 216, as explained in greater detail with respect to FIG. 3.

Referring now to FIG. 3, there is shown a schematic electrical circuitdiagram of a first embodiment electrode compensation circuit (indicatedgenerally at 300) housed within the test meter. As indicated, thecircuit couples to contact pads 214 b, 216 b and 224 b when the teststrip 200 is inserted into the test meter. As will be appreciated bythose skilled in the art, a voltage potential is applied to the counterelectrode contact pad 216 b, which will produce a current between thecounter electrode 216 a and the working electrode 214 a that isproportional to the amount of analyte present in the biological sampleapplied to the reagent 18. The current from working electrode 214 a istransmitted to working electrode contact pad. 214 b by means of workingelectrode trace 214 c and provided to a current-to-voltage amplifier310. The analog output voltage of amplifier 310 is converted to adigital signal by analog-to-digital converter (A/D) 312. This digitalsignal is then processed by microprocessor 314 according to a previouslystored program in order to determine the concentration of analyte withinthe biological sample applied to the test strip 200. This concentrationis displayed to the user by means of an appropriate output device 316,such as a liquid crystal display (LCD) screen.

Microprocessor 314 also outputs a digital signal indicative of thevoltage potential to be applied to the counter electrode contact pad 216b. This digital signal is converted to an analog voltage signal bydigital-to-analog converter (D/A) 318. The analog output of D/A 318 isapplied to a first input of an operational amplifier 320. A second inputof the operational amplifier 320 is coupled to counter sense electrodecontact pad 224 b. The output of operational amplifier 320 is coupled tothe counter electrode contact pad 216 b.

Operational amplifier 320 is connected in a voltage followerconfiguration, in which the amplifier will adjust its output (within itsphysical limits of operation) until the voltage appearing at its secondinput is equal to the commanded voltage appearing at its first input.The second input of operational amplifier 320 is a high impedance input,therefore substantially no current flows in counter sense line 224.Since substantially no current flows, any parasitic resistance incounter sense line 224 will not cause a potential drop, and the voltageappearing at the second input of operational amplifier 320 issubstantially the same as the voltage at counter sense electrode 224 a,which is in turn substantially the same as the voltage appearing atcounter electrode 216 a due to their close physical proximity.Operational amplifier 320 therefore acts to vary the voltage potentialapplied to the counter electrode contact pad 216 b until the actualvoltage potential appearing at the counter electrode 216 a (as fed backover counter sense line 224) is equal to the voltage potential commandedby the microprocessor 314. Operational amplifier 320 thereforeautomatically compensates for any potential drop caused by the parasiticresistance in the counter electrode trace 216 c, and the potentialappearing at the counter electrode 216 a is the desired potential. Thecalculation of the analyte concentration in the biological sample fromthe current produced by the working electrode is therefore made moreaccurate, since the voltage that produced the current is indeed the samevoltage commanded by the microprocessor 314. Without the compensationfor parasitic resistance voltage drops provided by the circuit 300, themicroprocessor 314 would analyze the resulting current under themistaken presumption that the commanded voltage was actually applied tothe counter electrode 216 a.

Many methods are available for preparing test strips having multipleelectrodes, such as carbon ink printing, silver paste silk-screening,scribing metalized plastic, electroplating, chemical plating, andphoto-chemical etching, by way of non-limiting example. One method ofpreparing a test strip having additional electrode sense lines asdescribed herein is by the use of laser ablation techniques. Examples ofthe use of these techniques in preparing electrodes for biosensors aredescribed in U.S. patent application Ser. No. 09/866,030, “Biosensorswith Laser Ablation Electrodes with a Continuous Coverlay Channel” filedMay 25, 2001, and in U.S. patent application Ser. No. 09/411,940,entitled “Laser Defined Features for Patterned Laminates and Electrode,”filed Oct. 4, 1999, both disclosures incorporated herein by reference.Laser ablation is useful in preparing test strips according to thepresent invention because it allows conductive areas having extremelysmall feature sizes to be accurately manufactured in a repeatablemanner. Laser ablation provides a means for adding the extra sense linesof the present invention to a test strip without increasing the size ofthe test strip.

It is desirable in the present invention to provide for the accurateplacement of the electrical components relative to one another and tothe overall biosensor. In one embodiment, the relative placement ofcomponents is achieved, at least in part, by the use of broad fieldlaser ablation that is performed through a mask or other device that hasa precise pattern for the electrical components. This allows accuratepositioning of adjacent edges, which is further enhanced by the closetolerances for the smoothness of the edges.

FIG. 4 illustrates a simple biosensor 401 useful for illustrating thelaser ablation process of the present invention, including a substrate402 having formed thereon conductive material 403 defining electrodesystems comprising a first electrode set 404 and a second electrode set405, and corresponding traces 406, 407 and contact pads 408, 409,respectively. Note that the biosensor 401 is used herein for purposes ofillustrating the laser ablation process, and that it is not shown asincorporating the sense lines of the present invention. The conductivematerial 403 may contain pure metals or alloys, or other materials,which are metallic conductors. In some embodiments, the conductivematerial is absorptive at the wavelength of the laser used to form theelectrodes and of a thickness amenable to rapid and precise processing.Non-limiting examples include aluminum, carbon, copper, chromium, gold,indium tin oxide (ITO), palladium, platinum, silver, tin oxide/gold,titanium, mixtures thereof, and alloys or metallic compounds of theseelements. In some embodiments, the conductive material includes noblemetals or alloys or their oxides. Other embodiments use conductivematerials such as gold, palladium, aluminum, titanium, platinum, ITO andchromium. The conductive material ranges in thickness from about 10 nmto 80 nm. Some embodiments use thickness ranges between 30 nm to 70 nm,others use thicknesses at 50 nm. It is appreciated that the thickness ofthe conductive material depends upon the transmissive property of thematerial and other factors relating to use of the biosensor.

While not illustrated, it is appreciated that the resulting patternedconductive material can be coated or plated with additional metallayers. For example, the conductive material may be copper, which isthen ablated with a laser into an electrode pattern; subsequently, thecopper may be plated with a titanium/tungsten layer, and then a goldlayer, to form the desired electrodes. In most embodiments, a singlelayer of conductive material is used, which lies on the base 402.Although not generally necessary, it is possible to enhance adhesion ofthe conductive material to the base, as is well known in the art, byusing seed or ancillary layers such as chromium nickel or titanium. Insome embodiments, biosensor 401 has a single layer of gold, palladium,platinum or ITO.

Biosensor 401 is illustratively manufactured using two apparatuses 10,10′, shown in FIGS. 4,6 and 7, respectively. It is appreciated thatunless otherwise described, the apparatuses 410, 410′ operate in asimilar manner. Referring first to FIG. 5, biosensor 401 is manufacturedby feeding a roll of ribbon 420 having an 80 nm gold laminate, which isabout 40 mm in width, into a custom fit broad field laser ablationapparatus 410. The apparatus 410 comprises a laser source 411 producinga beam of laser light 412, a chromium-plated quartz mask 414, and optics416. It is appreciated that while the illustrated optics 416 is a singlelens, optics 416 can be a variety of lenses that cooperate to make thelight 412 in a pre-determined shape.

A non-limiting example of a suitable ablation apparatus 410 (FIGS. 5-6)is a customized MicrolineLaser 200-4 laser system commercially availablefrom LPKF Laser Electronic GmbH, of Garbsen, Germany, which incorporatesan LPX-400, LPX-300 or LPX-200 laser system commercially available fromLambda Physik AG, Göttingen, Germany and a chromium-plated quartz maskcommercially available from Infinite Graphics, Minneapolis, Minn.

For the MicrolineLaser 200-4 laser system (FIGS. 5-6), the laser source411 is a LPX-200 KrF-UV-laser. It is appreciated, however, that higherwavelength UV lasers can be used in accordance with this disclosure. Thelaser source 411 works at 248 nm, with a pulse energy of 600 mJ, and apulse repeat frequency of 50 Hz. The intensity of the laser beam 412 canbe infinitely adjusted between 3% and 92% by a dielectric beamattenuator (not shown). The beam profile is 27×15 mm² (0.62 sq. inch)and the pulse duration 25 ns. The layout on the mask 414 ishomogeneously projected by an optical elements beam expander,homogenizer, and field lens (not shown). The performance of thehomogenizer has been determined by measuring the energy profile. Theimaging optics 416 transfer the structures of the mask 414 onto theribbon 420. The imaging ratio is 2:1 to allow a large area to be removedon the one hand, but to keep the energy density below the ablation pointof the applied chromium mask on the other hand. While an imaging of 2:1is illustrated, it is appreciated that the any number of alternativeratios are possible in accordance with this disclosure depending uponthe desired design requirements. The ribbon 420 moves as shown by arrow425 to allow a number of layout segments to be ablated in succession.

The positioning of the mask 414, movement of the ribbon 420, and laserenergy are computer controlled. As shown in FIG. 5, the laser beam 412is projected onto the ribbon 420 to be ablated. Light 412 passingthrough the clear areas or windows 418 of the mask 414 ablates the metalfrom the ribbon 420. Chromium coated areas 424 of the mask 414 blocksthe laser light 412 and prevent ablation in those areas, resulting in ametallized structure on the ribbon 420 surface. Referring now to FIG. 6,a complete structure of electrical components may require additionalablation steps through a second mask 414′. It is appreciated thatdepending upon the optics and the size of the electrical component to beablated, that only a single ablation step or greater than two ablationsteps may be necessary in accordance with this disclosure. Further, itis appreciated that instead of multiple masks, that multiple fields maybe formed on the same mask in accordance with this disclosure.

Specifically, a second non-limiting example of a suitable ablationapparatus 410′ (FIG. 7) is a customized laser system commerciallyavailable from LPKF Laser Electronic GmbH, of Garbsen, Germany, whichincorporates a Lambda STEEL (Stable energy eximer laser) laser systemcommercially available from Lambda Physik AG, Göttingen, Germany and achromium-plated quartz mask commercially available from InfiniteGraphics, Minneapolis, Minn. The laser system features up to 1000 mJpulse energy at a wavelength of 308 nm. Further, the laser system has afrequency of 100 Hz. The apparatus 410′ may be formed to producebiosensors with two passes as shown in FIGS. 5 and 6, but in someembodiments its optics permit the formation of a 10×40 mm pattern in a25 ns single pass.

While not wishing to be bound to a specific theory, it is believed thatthe laser pulse or beam 412 that passes through the mask 414, 414′, 414″is absorbed within less than 1 μm of the surface 402 on the ribbon 420.The photons of the beam 412 have an energy sufficient to causephoto-dissociation and the rapid breaking of chemical bonds at themetal/polymer interface. It is believed that this rapid chemical bondbreaking causes a sudden pressure increase within the absorption regionand forces material (metal film 403) to be ejected from the polymer basesurface. Since typical pulse durations are around 20-25 nanoseconds, theinteraction with the material occurs very rapidly and thermal damage toedges of the conductive material 403 and surrounding structures isminimized. The resulting edges of the electrical components have highedge quality and accurate placement as contemplated by the presentinvention.

Fluence energies used to remove or ablate metals from the ribbon 420 aredependent upon the material from which the ribbon 420 is formed,adhesion of the metal film to the base material, the thickness of themetal film, and possibly the process used to place the film on the basematerial, i.e. supporting and vapor deposition. Fluence levels for goldon KALADEX® range from about 50 to about 90 mJ/cm², on polyimide about100 to about 120 mJ/cm², and on MELINEX® about 60 to about 120 mJ/cm².It is understood that fluence levels less than or greater than the abovementioned can be appropriate for other base materials in accordance withthe disclosure.

Patterning of areas of the ribbon 420 is achieved by using the masks414, 414′. Each mask 414, 414′ illustratively includes a mask field 422containing a precise two-dimensional illustration of a pre-determinedportion of the electrode component patterns to be formed. FIG. 5illustrates the mask field 422 including contact pads and a portion oftraces. As shown in FIG. 6, the second mask 414′ contains a secondcorresponding portion of the traces and the electrode patternscontaining fingers. As previously described, it is appreciated thatdepending upon the size of the area to be ablated, the mask 414 cancontain a complete illustration of the electrode patterns (FIG. 7), orportions of patterns different from those illustrated in FIGS. 5 and 6in accordance with this disclosure. It is contemplated that in oneaspect of the present invention, the entire pattern of the electricalcomponents on the test strip are laser ablated at one time, i.e., thebroad field encompasses the entire size of the test strip (FIG. 7). Inthe alternative, and as illustrated in FIGS. 5 and 6, portions of theentire biosensor are done successively.

While mask 414 will be discussed hereafter, it is appreciated thatunless indicated otherwise, the discussion will apply to masks 414′,414″ as well. Referring to FIG. 5, areas 424 of the mask field 422protected by the chrome will block the projection of the laser beam 412to the ribbon 420. Clear areas or windows 418 in the mask field 422allow the laser beam 412 to pass through the mask 414 and to impactpredetermined areas of the ribbon 420. As shown in FIG. 5, the cleararea 418 of the mask field 422 corresponds to the areas of the ribbon420 from which the conductive material 403 is to be removed.

Further, the mask field 422 has a length shown by line 430 and a widthas shown by line 432. Given the imaging ratio of 2:1 of the LPX-200, itis appreciated that the length 30 of the mask is two times the length ofa length 434 of the resulting pattern and the width 432 of the mask istwo times the width of a width 436 of the resulting pattern on ribbon420. The optics 416 reduces the size of laser beam 412 that strikes theribbon 420. It is appreciated that the relative dimensions of the maskfield 422 and the resulting pattern can vary in accordance with thisdisclosure. Mask 414′ (FIG. 6) is used to complete the two-dimensionalillustration of the electrical components.

Continuing to refer to FIG. 5, in the laser ablation apparatus 410 theexcimer laser source 411 emits beam 412, which passes through thechrome-on-quartz mask 414. The mask field 422 causes parts of the laserbeam 412 to be reflected while allowing other parts of the beam to passthrough, creating a pattern on the gold film where impacted by the laserbeam 412. It is appreciated that ribbon 420 can be stationary relativeto apparatus 410 or move continuously on a roll through apparatus 410.Accordingly, non-limiting rates of movement of the ribbon 420 can befrom about 0 m/min to about 100 m/min, and in some embodiments about 30m/min to about 60 m/min. It is appreciated that the rate of movement ofthe ribbon 420 is limited only by the apparatus 410 selected and maywell exceed 100 m/min depending upon the pulse duration of the lasersource 411 in accordance with the present disclosure.

Once the pattern of the mask 414 is created on the ribbon 420, theribbon is rewound and fed through the apparatus 410 again, with mask414′ (FIG. 6). It is appreciated, that alternatively, laser apparatus410 could be positioned in series in accordance with this disclosure.Thus, by using masks 414, 414′, large areas of the ribbon 420 can bepatterned using step-and-repeat processes involving multiple mask fields422 in the same mask area to enable the economical creation of intricateelectrode patterns and other electrical components on a substrate of thebase, the precise edges of the electrode components, and the removal ofgreater amounts of the metallic film from the base material.

The second embodiment of the present invention illustrated in FIGS. 8and 9 improve upon the prior art by providing for I-R drop compensationof both the working and counter electrode leads on the test strip.Referring now to FIG. 8, there is schematically illustrated a secondembodiment test strip configuration of the present invention, indicatedgenerally at 800. The test strip 800 comprises a bottom substrate 12coated on its top surface with a 50 nm conductive gold layer (forinstance by sputtering or vapor deposition, by way of non-limitingexample). Electrodes, connecting traces and contact pads therefor arethen patterned in the conductive layer by a laser ablation process asdescribed hereinabove. For example, working 814 a, working sense 826 a,counter 216 a, and counter sense 224 a electrodes may be formed as shownand coupled to respective measurement contact pads 814 b, 826 b, 216 band 224 b by means of respective traces 814 c, 826 c, 216 c and 224 c.These contact pads 814 b, 826 b, 216 b and 224 b provide a conductivearea upon the test strip 800 to be contacted by a connector contact ofthe test meter (not shown) once the test strip 800 is inserted into thetest meter.

It will be appreciated that the test strip 800 of FIG. 8 issubstantially identical to the first embodiment test strip 200 of FIG.2, except for the addition of the working sense electrode 826 a, contactpad 826 b, and trace 826 c. Provision of the working sense line 826allows the test meter to compensate for any I-R drop caused by thecontact resistance of the connections to the contact pads 814 b and 216b, and to compensate for the trace resistance of traces 814 c and 216 c.

Referring now to FIG. 9, there is shown a schematic electrical circuitdiagram of a second embodiment electrode compensation circuit (indicatedgenerally at 900) housed within the test meter. As indicated, thecircuit couples to contact pads 826 b, 814 b, 216 b and 224 b when thetest strip 800 is inserted into the test meter. As will be appreciatedby those skilled in the art, a voltage potential is applied to thecounter electrode contact pad 216 b, which will produce a currentbetween the counter electrode 216 a and the working electrode 814 a thatis proportional to the amount of analyte present in the biologicalsample applied to the reagent 18. The current from working electrode 814a is transmitted by working electrode trace 814 c to working electrodecontact pad 814 b and provided to current-to-voltage amplifier 310. Theanalog output voltage of amplifier 310 is converted to a digital signalby A/D 312. This digital signal is then processed by microprocessor 314according to a previously stored program in order to determine theconcentration of the analyte of interest within the biological sampleapplied to the test strip 800. This concentration is displayed to theuser by means of LCD output device 316.

Microprocessor 314 also outputs a digital signal indicative of thevoltage potential to be applied to the counter electrode contact pad 216b. This digital signal is converted to an analog voltage signal by D/A318. The analog output of D/A 318 is applied to a first input of anoperational amplifier 320. A second input of the operational amplifier320 is coupled to an output of operational amplifier 910. Operationalamplifier 910 is connected in a difference amplifier configuration usingan instrumentation amplifier. A first input of operational amplifier 910is coupled to working sense electrode contact pad 826 b, while a secondinput of operational amplifier 910 is coupled to counter sense electrodecontact pad 224 b. The output of operational amplifier 320 is coupled tothe counter electrode contact pad 216 b.

Operational amplifier 320 is connected in a voltage followerconfiguration, in which the amplifier will adjust its output (within itsphysical limits of operation) until the voltage appearing at its secondinput is equal to the commanded voltage appearing at its first input.Both inputs of operational amplifier 910 are high impedance inputs,therefore substantially no current flows in counter sense line 224 orworking sense line 826. Since substantially no current flows, anyparasitic resistance in counter sense line 224 or working sense line 826will not cause a potential drop, and the voltage appearing across theinputs of operational amplifier 910 is substantially the same as thevoltage across the measurement cell (i.e. across counter electrode 216 aand working electrode 814 a). Because operational amplifier 910 isconnected in a difference amplifier configuration, its output representsthe voltage across the measurement cell.

Operational amplifier 320 will therefore act to vary its output (i.e.the voltage potential applied to the counter electrode contact pad 216b) until the actual voltage potential appearing across the measurementcell is equal to the voltage potential commanded by the microprocessor314. Operational amplifier 320 therefore automatically compensates forany potential drop caused by the parasitic resistance in the counterelectrode trace 216 c, counter electrode contact 216 b, workingelectrode trace 814 c, and working electrode contact 814 b, andtherefore the potential appearing across the measurement cell is thedesired potential. The calculation of the analyte concentration in thebiological sample from the current produced by the working electrode istherefore made more accurate.

FIG. 10, in conjunction with FIG. 8, illustrates a third embodiment ofthe present invention that improves over the prior art by providing I-Rdrop compensation for both the working and counter electrode lines, aswell as providing verification that the resistance of both the workingand counter electrode lines is not above a predetermined threshold inorder to assure that the test meter is able to compensate for the I-Rdrops. Referring now to FIG. 10, there is shown a schematic electricalcircuit diagram of a third embodiment electrode compensation circuit(indicated generally at 1000) housed within the test meter. Theelectrode compensation circuit 1000 works with the test strip 800 ofFIG. 8. As indicated, the circuit couples to contact pads 826 b, 814 b,216 b and 224 b when the test strip 800 is inserted into the test meter.As will be appreciated by those skilled in the art, a voltage potentialis applied to the counter electrode contact pad 216 b, which willproduce a current between the counter electrode 216 a and the workingelectrode 814 a that is proportional to the amount of analyte present inthe biological sample applied to the reagent 18. The current fromworking electrode 814 a is transmitted to working electrode contact pad814 b by working electrode trace 814 c and provided tocurrent-to-voltage amplifier 310. The output of current-to-voltageamplifier 310 is applied to the input of instrumentation amplifier 1002which is configured as a buffer having unity gain when switch 1004 inthe closed position. The analog output voltage of amplifier 1002 isconverted to a digital signal by A/D 312. This digital signal is thenprocessed by microprocessor 314 according to a previously stored programin order to determine the concentration of analyte within the biologicalsample applied to the test strip 800. This concentration is displayed tothe user by means of LCD output device 316.

Microprocessor 314 also outputs a digital signal indicative of thevoltage potential to be applied to the counter electrode contact pad 216b. This digital signal is converted to an analog voltage signal by D/A318. The analog output of D/A 318 is applied to the input of anoperational amplifier 320 that is configured as a voltage follower whenswitch 1006 is in the position shown. The output of operationalamplifier 320 is coupled to the counter electrode contact pad 216 b,which will allow measurement of a biological fluid sample applied to thereagent 18. Furthermore, with switches 1006, 1008 and 1010 positioned asillustrated in FIG. 10, the circuit is configured as shown in FIG. 9 andmay be used to automatically compensate for parasitic and contactresistance as described hereinabove with respect to FIG. 9.

In order to measure the amount of parasitic resistance in the counterelectrode line 216, switch 1008 is placed in the position shown in FIG.10, switch 1006 is placed in the position opposite that shown in FIG.10, while switch 1010 is closed. The operational amplifier 320 thereforeacts as a buffer with unity gain and applies a voltage potential tocounter electrode contact pad 216 b through a known resistance R_(nom).This resistance causes a current to flow in the counter electrode line216 and the counter sense line 224 that is sensed by current-to-voltageamplifier 310, which is now coupled to the current sense line throughswitch 1010. The output of current-to-voltage amplifier 310 is providedto the microprocessor 314 through AID 312. Because the value of R_(nom)is known, the microprocessor 314 can calculate the value of anyparasitic resistance in the counter sense line 224 and the counterelectrode line 216. This parasitic resistance value can be compared to apredetermined threshold stored in the test meter to determine ifphysical damage has occurred to the test strip 800 or if nonconductivebuildup is present on the contact pads to such an extent that the teststrip 800 cannot be reliably used to perform a test. In such situations,the test meter may be programmed to inform the user that an alternatetest strip should be inserted into the test meter before proceeding withthe test.

In order to measure the amount of parasitic resistance in the workingelectrode line 814, switches 1006 and 1008 are placed in the positionopposite that shown in FIG. 10, while switch 1010 is opened. Theoperational amplifier 320 therefore acts as a buffer with unity gain andapplies a voltage potential to working sense contact pad 826 b through aknown resistance R_(nom). This resistance causes a current to flow inthe working sense line 826 and the working electrode line 814 that issensed by current-to-voltage amplifier 310. The output ofcurrent-to-voltage amplifier 310 is provided to the microprocessor 314through A/D 312. Because the value of R_(nom) is known, themicroprocessor 314 can calculate the value of any parasitic resistancein the working sense line 826 and the working electrode line 814. Thisparasitic resistance value can be compared to a predetermined thresholdstored in the test meter to determine if physical damage has occurred tothe test strip 800 or if nonconductive buildup is present on the contactpads to such an extent that the test strip 800 cannot be reliably usedto perform a test. In such situations, the test meter may be programmedto inform the user that an alternate test strip should be inserted intothe test meter before proceeding with the test.

FIG. 11 schematically illustrates a third embodiment test stripaccording to the present invention having I-R drop compensation for boththe working electrode and the counter electrode as in FIG. 8. The thirdembodiment test strip 1100 comprises a bottom substrate 12 coated on itstop surface with a 50 nm conductive layer (for instance by sputtering orvapor deposition, by way of non-limiting example). Electrodes,connecting traces and contact pads therefor are then patterned in theconductive layer by a laser ablation process as described hereinabove.As will readily be apparent to those skilled in the art, the test stripof FIG. 11 is similar to the test strip of FIG. 8. Unlike the test stripof FIG. 8, the counter sense line 224 and the working sense line 826 donot extend into the reaction zone 20. In addition, the counter electrode216 a includes a plurality of fingers 1104 instead of just one. In otherembodiments, the working electrode 814 a also can include a plurality offingers 1104. Moreover, a capillary space 1102 is provided for drawingthe sample into the reaction zone 20 so that it covers portions of theelectrodes 216 a and 814 a.

The design illustrated in FIG. 11 inherently includes some performancelimitations. Lines A-A, B-B, C-C, etc. are areas that cannot beinterrogated to determine if there are faults in the structuralintegrity of the electrodes 216 a, 814 a or the fingers 1104. Forexample, any physical defect in these areas, such as a scratch thatincreases the trace resistance or completely severs the trace cannot bedetected by the quality assurance checks described hereinabove. This isdue to the fact that the sense lines 224 c, 826 c join respectiveelectrode traces 216 c, 814 c at points between the test meter and lineA-A. Any damage to the test strip 1100 between lines A-A and F-F istherefore outside of the quality assurance test loop and will have noimpact upon the I-R drop compensation or parasitic resistance thresholdtest described hereinabove. The position of the sense lines 826, 224therefore prevent complete testing of the functionality of the teststrip 1100 before a fluid sample is obtained and analyzed. Therefore,the final measurement of the desired characteristic of the fluid samplemay be erroneous.

FIG. 12 illustrates a more robust test strip design to overcome theshortcomings of the design illustrated in FIG. 11. The test strip 1200includes a working sense line 826 and a counter sense line 224 that haverespective points 1206, 1208 where they intersect respective electrodes814 a, 216 a. Working sense line 826 and counter sense line 224 areconductive traces formed on substrate 12. The distance (measured in aplane parallel to the longitudinal axis of the test strip) between point1206 and the power source in the test meter for the test strip 1200 isgreater than or equal to the distance between any point on the portionof the working electrode 814 a within the reagent 18 and the powersource. Similarly, the distance between point 1208 and the power sourcefor the test strip 1200 is greater than or equal to the distance betweenany point on the portion of the counter electrode 216 a within thereagent 18 and the power source. Having working sense line 826 andcounter sense line 224 include points 1206, 1208 at these locationsenables every point on the test strip 1200 between the power source andthe measurement electrode fingers to be interrogated concerning itsstructural integrity and parasitic resistance. Unlike the design in FIG.11, the design in FIG. 12 positions the sense lines 224, 826 to enableinterrogation of the electrodes 216 a, 814 a and associated fingers forstructural defects. If a defect is found, it can be compensated for orit can be indicated and the test strip 1200 can be disposed of and a newone used. This helps to eliminate errors in the measurement of thedesired characteristic of the fluid sample.

All publications, prior applications, and other documents cited hereinare hereby incorporated by reference in their entirety as if each hadbeen individually incorporated by reference and fully set forth.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, the description is to be consideredas illustrative and not restrictive in character. Only certainembodiments deemed helpful in understanding have been shown. All changesand modifications that come within the spirit of the invention aredesired to be protected.

1. An electrochemical test strip powered by a power source comprising: afirst measurement electrode; a first conductive trace operativelycoupled to the first measurement electrode, wherein the distance betweenat least one point on the first conductive trace and the power source isgreater than or equal to the distance between any point on said firstmeasurement electrode and the power source; a second measurementelectrode; and a second conductive trace operatively coupled to thesecond measurement electrode; wherein the distance between at least onepoint on the second conductive trace and the power source is greaterthan or equal to the distance between any point on said secondmeasurement electrode and the power source.
 2. The test strip of claim 1wherein said first measurement electrode comprises a plurality offingers.
 3. The test strip of claim 1 wherein said second measurementelectrode comprises a plurality of fingers.
 4. The test strip of claim 2wherein said fingers include a reagent to create an electrical potentialin a fluid sample that is indicative of a desired fluid quality to bemeasured by the test strip.
 5. The test strip of claim 3 wherein saidfingers include a reagent to create an electrical potential in a fluidsample that is indicative of a desired fluid quality to be measured bythe test strip.
 6. An electrochemical test strip powered by a powersource comprising: a measurement electrode; a conductive traceoperatively coupled to the measurement electrode, wherein the distancebetween at least one point on the conductive trace and the power sourceis greater than or equal to the distance between any point on saidmeasurement electrode and the power source.
 7. The test strip of claim 6wherein said measurement electrode comprises a plurality of fingers. 8.The test strip of claim 6 further comprising an additional measurementelectrode.
 9. The test strip of claim 8 further comprising an additionalconductive trace operatively coupled to said additional measurementelectrode.
 10. The test strip of claim 7 wherein said fingers furthercomprise a reagent to create an electrical potential in a fluid samplethat is indicative of a desired fluid quality to be measured by the teststrip.
 11. An electrochemical test strip powered by a power sourcecomprising: a reagent diposed within a region on the test strip; a firstmeasurement electrode; a first conductive trace operatively coupled tothe first measurement electrode, wherein the distance between at leastone point on the first conductive trace and the power source is greaterthan or equal to the distance between any point on said firstmeasurement electrode within said region and the power source; a secondmeasurement electrode; and a second conductive trace operatively coupledto the second measurement electrode, wherein the distance between atleast one point on the second conductive trace and the power source isgreater than or equal to the distance between any point on said secondmeasurement electrode within said region and the power source.
 12. Thetest strip of claim 11 wherein said first measurement electrodecomprises a plurality of fingers.
 13. The test strip of claim 11 whereinsaid second measurement electrode comprises a plurality of fingers. 14.An electrochemical test strip powered by a power source comprising: areagent disposed within a region on the test strip; a measurementelectrode; a conductive trace operatively coupled to the measurementelectrode, wherein the distance between at least one point on theconductive trace and the power source is greater than or equal to thedistance between any point on said measurement electrode within saidregion and the power source.
 15. The test strip of claim 14 wherein saidmeasurement electrode comprises a plurality of fingers.
 16. The teststrip of claim 14 further comprising an additional measurementelectrode.
 17. The test strip of claim 16 further comprising anadditional conductive trace operatively coupled to said additionalmeasurement electrode.